Disease progression models infer group-level temporal trajectories of change in patients' features as a chronic degenerative condition plays out.

Models of disease progression are instrumental forpredictingpatient outcomes and understandingdisease dynamics. Existing models provide the patient with pragmatic (supervised) predictions of risk, but do not provide the clinician with intelligible (unsupervised) representations ofdiseasepathology.

Predicting Parkinson's Disease (PD) progression is crucial, and voice biomarkers offer a non-invasive method for tracking symptom severity (UPDRS scores) through telemonitoring. Analyzing this longitudinal data is challenging due to within-subject correlations and complex, nonlinear patient-specific progression patterns. This study benchmarks LMMs against two advanced hybrid approaches: the Generalized Neural Network Mixed Model (GNMM) (Mandel 2021), which embeds a neural network within a GLMM structure, and the Neural Mixed Effects (NME) model (Wortwein 2023), allowing nonlinear subject-specific parameters throughout the network. Using the Oxford Parkinson's telemonitoring voice dataset, we evaluate these models' performance in predicting Total UPDRS to offer practical guidance for PD research and clinical applications.

Disease progression models infer group-level temporal trajectories of change in patients' features as a chronic degenerative condition plays out. They provide unique insight into disease biology and staging systems with individual-level clinical utility. Discrete models consider disease progression as a latent permutation of events, where each event corresponds to a feature becoming measurably abnormal. However, permutation inference using traditional maximum likelihood approaches becomes prohibitive due to combinatoric explosion, severely limiting model dimensionality and utility. Here we leverage ideas from optimal transport to model disease progression as a latent permutation matrix of events belonging to the Birkhoff polytope, facilitating fast inference via optimisation of the variational lower bound. This enables a factor of 1000 times faster inference than the current state of the art and, correspondingly, supports models with several orders of magnitude more features than the current state of the art can consider. Experiments demonstrate the increase in speed, accuracy and robustness to noise in simulation.

Models of disease progression are instrumental for predicting patient outcomes and understanding disease dynamics. Existing models provide the patient with pragmatic (supervised) predictions of risk, but do not provide the clinician with intelligible (unsupervised) representations of disease pathophysiology. In this paper, we develop the attentive state-space model, a deep probabilistic model that learns accurate and interpretable structured representations for disease trajectories. Unlike Markovian state-space models, in which the dynamics are memoryless, our model uses an attention mechanism to create memoryful dynamics, whereby attention weights determine the dependence of future disease states on past medical history. To learn the model parameters from medical records, we develop an infer ence algorithm that simultaneously learns a compiled inference network and the model parameters, leveraging the attentive state-space representation to construct a Rao-Blackwellized variational approximation of the posterior state distribution. Experiments on data from the UK Cystic Fibrosis registry show that our model demonstrates superior predictive accuracy and provides insights into the progression of chronic disease.

Chronic diseases often progress differently across patients. Rather than randomly varying, there are typically a small number of subtypes for how a disease progresses across patients. To capture this structured heterogeneity, the Subtype and Stage Inference Event-Based Model (SuStaIn) estimates the number of subtypes, the order of disease progression for each subtype, and assigns each patient to a subtype from primarily cross-sectional data. It has been widely applied to uncover the subtypes of many diseases and inform our understanding of them. But how robust is its performance? In this paper, we develop a principled Bayesian subtype variant of the event-based model (BEBMS) and compare its performance to SuStaIn in a variety of synthetic data experiments with varied levels of model misspecification. BEBMS substantially outperforms SuStaIn across ordering, staging, and subtype assignment tasks. Further, we apply BEBMS and SuStaIn to a real-world Alzheimer's data set. We find BEBMS has results that are more consistent with the scientific consensus of Alzheimer's disease progression than SuStaIn.

Alzheimer's disease (AD), a degenerative brain condition, can benefit from early prediction to slow its progression. As the disease progresses, patients typically undergo brain atrophy. Current prediction methods for Alzheimers disease largely involve analyzing morphological changes in brain images through manual feature extraction. This paper proposes a novel method, the Deformation-Aware Temporal Generative Network (DATGN), to automate the learning of morphological changes in brain images about disease progression for early prediction. Given the common occurrence of missing data in the temporal sequences of MRI images, DATGN initially interpolates incomplete sequences. Subsequently, a bidirectional temporal deformation-aware module guides the network in generating future MRI images that adhere to the disease's progression, facilitating early prediction of Alzheimer's disease. DATGN was tested for the generation of temporal sequences of future MRI images using the ADNI dataset, and the experimental results are competitive in terms of PSNR and MMSE image quality metrics. Furthermore, when DATGN-generated synthetic data was integrated into the SVM vs. CNN vs. 3DCNN-based classification methods, significant improvements were achieved from 6. 21\% to 16\% in AD vs. NC classification accuracy and from 7. 34\% to 21. 25\% in AD vs. MCI vs. NC classification accuracy. The qualitative visualization results indicate that DATGN produces MRI images consistent with the brain atrophy trend in Alzheimer's disease, enabling early disease prediction.